We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
FUS-Immunoreactive Intranuclear Inclusions in Neurodegenerative Disease.
- Authors
Woulfe, John; Gray, Douglas A.; Mackenzie, Ian R.A.
- Abstract
Neuronal intranuclear inclusions (NIIs) are a histopathological hallmark of several neurodegenerative disorders. However, the role played by NIIs in neurodegenerative pathogenesis remains enigmatic. Defining their molecular composition represents an important step in understanding the pathophysiology of these disorders. Recently, a nuclear protein, “fused-in-sarcoma” (FUS) was identified as the pathological protein in two forms of frontotemporal lobar degeneration (FTLD-IF, formerly known as neuronal intermediate filament inclusion disease, and FTLD-UPS, formerly known as atypical FTLD-U), both of which are characterized by the presence of NII. The objective of the present study was to determine the range of neurodegenerative disorders characterized by FUS-positive NIIs. Immunostaining for FUS revealed intense reactivity of NIIs in FTLD-IF and FTLD-UPS as well as in Huntington's disease, spinocerebellar ataxias 1 and 3, and neuronal intranuclear inclusion body disease. In contrast, there was no FUS staining of NIIs in inherited forms of FTLD-TDP caused by GRN and VCP mutations, fragile-X-associated tremor ataxia syndrome, or oculopharyngeal muscular dystrophy. In a cell culture model of Huntington's disease, NIIs were intensely FUS-positive. NII-bearing cells displayed loss of the normal diffuse nuclear pattern of FUS staining. This suggests that sequestration of nuclear FUS by NIIs may interfere with its normal nuclear localization.
- Subjects
NEURODEGENERATION; HUNTINGTON disease; CARCINOGENESIS; NUCLEAR proteins; SARCOMA; FRIEDREICH'S ataxia; CELL culture
- Publication
Brain Pathology, 2010, Vol 20, Issue 3, p589
- ISSN
1015-6305
- Publication type
Article
- DOI
10.1111/j.1750-3639.2009.00337.x